Our goal for this project is to design and synthesize novel peptide and peptidomimetic inhibitors, specifically targeted against proteases central to the pathogenesis of malaria, schistosomiasis and hepatitis A. In the absence of X-ray structure of cysteine protease of our interest, we have simulated the enzyme model based on sequence homology to other cysteine proteases. We have designed and synthesized a wide variety of chemical compounds which include heteroaromatic inhibitors, peptide-based and peptidomimetic inhibitors. Mass spectrometry has played an important role in assoication with 1NMR, 13C NMR, 19F NMR and 31P NMR in characterizing these lead compounds of diverse chemical nature and background. MassSpectrometry will remain an integral part of our research in analyzing the next generation of inhibitors.